Objective:To evaluate the feasibility, safety, and clinical outcomes of full-time full-endoscopic lumbar interbody fusion (FELIF) using a bladed retractor fusion channel (BRFC) system with reversed-mounting designed instruments compared to a tubular fusion channel (TFC).Methods:This retrospective study analyzed 101 cases of uniportal coaxial endoscopic lumbar interbody fusion performed between June 2018 and April 2023. Based on the type of fusion channel utilized, patients were divided into the TFC group (59 cases) and the BRFC group (42 cases). The BRFC technique involved neurological decompression, endplate preparation, and interbody fusion performed under full-time endoscopic monitoring with reversed-mounting designed instruments. Key parameters, including surgery duration, intraoperative estimated blood loss (IEBL), complication incidence, and interbody fusion rate (assessed by Bridwell criteria), were compared between the two groups. Clinical outcomes, including visual analog scale (VAS) scores for back and leg pain, Japanese Orthopaedic Association (JOA) scores, and Oswestry Disability Index (ODI), were recorded preoperatively, postoperatively, and at the final follow-up. Additionally, disc height at the fusion level was measured at one week postoperatively.Results:The mean follow-up duration was 42.9±12.1 months in the TFC group and 20.9±4.9 months in the BRFC group. No statistically significant differences were observed between the two groups in terms of surgery duration, IEBL, complication incidence, or interbody fusion rate (Grade 1 or 2 by Bridwell criteria) ( P>0.05). For single-level cases, the TFC group showed significantly better short-term clinical outcomes than the BRFC group at one week postoperatively, with JOA scores of 23(20, 25) versus 20(18, 23) ( Z=3.020, P=0.003) and ODI scores of 16%(11%, 21%) versus 28%(21%, 41%) ( Z=4.740, P<0.001). For double-level cases, the JOA score in the TFC group [23(20, 25)] was also significantly better than that in the BRFC group [20(18, 21)] ( Z=2.054, P=0.040) at one week postoperatively. However, at the final follow-up, all clinical indicators showed no significant differences between the two groups ( P>0.05). The disc height at the fusion level significantly increased at one week postoperatively compared to preoperative measurements in both groups ( P<0.05). However, the BRFC group demonstrated a significantly more recovery of disc height at one week postoperatively [(1.46±0.28) cm] compared to the TFC group [(1.17±0.20) cm] ( t=5.947, P<0.001). Conclusion:Full-time FELIF using the BRFC system and reversed-mounting designed instruments is a feasible, safe, and effective approach. However, its short-term clinical outcomes appear inferior to traditional FELIF using the TFC system.

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Objective:To evaluate the feasibility, safety, and clinical outcomes of full-time full-endoscopic lumbar interbody fusion (FELIF) using a bladed retractor fusion channel (BRFC) system with reversed-mounting designed instruments compared to a tubular fusion channel (TFC).Methods:This retrospective study analyzed 101 cases of uniportal coaxial endoscopic lumbar interbody fusion performed between June 2018 and April 2023. Based on the type of fusion channel utilized, patients were divided into the TFC group (59 cases) and the BRFC group (42 cases). The BRFC technique involved neurological decompression, endplate preparation, and interbody fusion performed under full-time endoscopic monitoring with reversed-mounting designed instruments. Key parameters, including surgery duration, intraoperative estimated blood loss (IEBL), complication incidence, and interbody fusion rate (assessed by Bridwell criteria), were compared between the two groups. Clinical outcomes, including visual analog scale (VAS) scores for back and leg pain, Japanese Orthopaedic Association (JOA) scores, and Oswestry Disability Index (ODI), were recorded preoperatively, postoperatively, and at the final follow-up. Additionally, disc height at the fusion level was measured at one week postoperatively.Results:The mean follow-up duration was 42.9±12.1 months in the TFC group and 20.9±4.9 months in the BRFC group. No statistically significant differences were observed between the two groups in terms of surgery duration, IEBL, complication incidence, or interbody fusion rate (Grade 1 or 2 by Bridwell criteria) ( P>0.05). For single-level cases, the TFC group showed significantly better short-term clinical outcomes than the BRFC group at one week postoperatively, with JOA scores of 23(20, 25) versus 20(18, 23) ( Z=3.020, P=0.003) and ODI scores of 16%(11%, 21%) versus 28%(21%, 41%) ( Z=4.740, P<0.001). For double-level cases, the JOA score in the TFC group [23(20, 25)] was also significantly better than that in the BRFC group [20(18, 21)] ( Z=2.054, P=0.040) at one week postoperatively. However, at the final follow-up, all clinical indicators showed no significant differences between the two groups ( P>0.05). The disc height at the fusion level significantly increased at one week postoperatively compared to preoperative measurements in both groups ( P<0.05). However, the BRFC group demonstrated a significantly more recovery of disc height at one week postoperatively [(1.46±0.28) cm] compared to the TFC group [(1.17±0.20) cm] ( t=5.947, P<0.001). Conclusion:Full-time FELIF using the BRFC system and reversed-mounting designed instruments is a feasible, safe, and effective approach. However, its short-term clinical outcomes appear inferior to traditional FELIF using the TFC system.

Objective:To investigate the drug resistance status and genomic characterization of Proteus mirabilis (PM) isolated from outpatient cases with diarrhea in Tai′an City and Laizhou City, Shandong Province. Methods:A total of 510 fecal samples were collected from 510 patients with acute diarrhea admitted to 43 sentinel hospitals in Tai′an City and Laizhou City, Shandong Province, between January 2021 and December 2022. The samples were cultured and isolated to identify Proteus spp. by direct inoculation, the drug susceptibility testing was performed by microbroth dilution method, and resistance genes and virulence genes were obtained by whole genome sequencing and bioinformatic analysis, thereby revealing the genetic environment surrounding the blaOXA-1 and blaCTX-M-65 genes. Single nucleotide polymorphism (SNP) analysis and core genome multilocus sequence typing (cgMLST) were conducted on the current strains and 100 PM isolates downloaded from the National Center for Biotechnology Information (NCBI) database via customizable methods utilizing RidomSeqSphere+ software, with the objective of exploring the phylogenetic relationships among the strains. Results:A total of 35 strains of Proteus were isolated from 510 fecal samples, including 31 strains of PM with a detection rate of 6.08% (31/510) and four strains of Proteus vulgaris.The multidrug resistance rate of PM was 100.00% (31/31).The 35 isolates carried a total of 43 resistance genotypes.Thirteen strains of PM carried blaOXA-1, six strains carried both blaOXA-1 and blaCTX-M-65, and 15 PM strains carried at least 15 antibiotic resistance genes (ARGs). The virulence genes included ureA, mrpA, ZapA, hpmA and so on. blaOXA-1 and blaCTX-M-65 genes were surrounded by mobile elements such as Tn3, ISL3 and IS6. cgMLST showed consistency with the SNP clustering results. Isolate 2022LZ41 from Laizhou City clustered with isolates 2022TA018, 2022TA017 and 2022TA019 from Tai′an City, with the number of allelic differences ranging from zero to two, and the Laizhou City isolate 2022LZ40 was highly genetically related to strain CRK0056 (human, USA, 2015). Conclusions:PM isolated from patients with diarrhea is multidrug-resistant, carrying many resistance and virulence genes.The presence of mobile genetic elements can lead to horizontal transfer of resistance genes.

Objective To explore risk factors of poor early prognosis in the treatment of COVID-19 by nematevir and ritonavir tablets Paxlovid and establish the prediction model to provide reference for improving the effect of such patients. Methods 92 inpatients of COVID-19 treated with Paxlovid in three military tertiary hospital in southern Fujian from January 2023 to March 2023 were retrospectively analyzed. The clinical indicators of 92 inpatients were collected for univariate and multivariate analysis by single factor and multiple factors and the independent risk factors of poor early prognosis in Paxlovid were screened out. Logistic model equation was transformed to construct the combined predictors, and ROC curve was used to determine the area under the curve (AUC) and the optimal critical value of the combined predictors. Results Among 92 patients, 31 (33.70%) developed poor early prognosis, including 11 deaths (35.48%), 17 critical cases (54.84%) and 3 severe cases (9.68%). Multi-factor Logistic regression analysis showed that the disease days, lymphocyte count, aspartate aminotransferase(AST), C reactive protein(CRP) and ventilator-assisted ventilation were independent risk factors for poor early prognosis in Paxlovid. A formula for calculating the combined predictors (Y) was established as Y_{combinedpredictors}=7.875X_{disease days}+126.188X_{lymphocyte count}+1.438X_AST+X_CRP+220.500X_{ventilator-assisted ventilation} based on the above independent risk factors, and the ROC curve was drawn. With the maximum area under the ROC curve of the combined predictors being 0.939, the prediction value was best, and the optimal critical value of the ROC curve corresponding to the maximum Youden index (0.756) was 447.920.Theoretical accuracy of the model was 89.10%. Conclusion The disease days, lymphocyte count, AST, CRP and ventilator-assisted ventilation were independent risk factors for poor early prognosis in Paxlovid. Combined predictors could be calculated by the above risk factors before medication. The efficiency should be improved by taking more active treatment, including combining with other anti-COVID-19 drugs when the prediction result exceeds 447.920.

Objective:Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods:We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results:In the analysis,average levels of indoor PM with aerodynamic diameters＜2.5 μm(PM2.5)decreased significantly by 59.2％(from 59.6 to 24.3 μg/m3,P＜0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by-84.6％(95％confidence interval[CI]:-90.7 to-78.6),growth differentiation factor-15 by-48.1％(95％CI:-31.2 to-25.6),osteoprotegerin by-65.4％(95％CI:-56.5 to-18.7),interleukin-4 by-46.6％(95％CI:-62.3 to-31.0)and myeloperoxidase by-60.3％(95％CI:-83.7 to-3.0),respectively.Conclusion:Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable popu-lations at risks.

Bacterial ghosts are bacterial cell envelopes devoid of cytoplasmic contents while maintaining their cellular morphology, which can be used as a new vaccine and delivery vector. In this study, a clinical isolate of avian pathogenic Escherichia coli (APEC) strain DE17 was used to prepare bacterial ghost through three different ways. The results showed that the cleavage efficiency of DE17 bacterial ghost was 99.9% with the lysis plasmid containing the PhiX174 lysis gene E. Scanning electron microscopy showed that transmembrane tunnels were formed in the middle or both ends of the cell envelope of DE17. Furthermore, the DE17 bacterial ghost was prepared with one of cell penetrating peptides (CPPs) named MAP (KLALKLALKALKAALKLA), which will completely inactivate DE17 (OD₆₀₀=0.1) by 10 μmol/L MAP. The cell envelope showed a gully-like structure and obvious transmembrane tunnels were not found through the SEM. However, the DE17 could not be lysed by importing the lysis plasmid (pBV220-MAP), which was used to express MAP. The present study will benefit for research on bacterial ghost preparation methods and provide a reference for biosafety of bacterial ghost vaccines.

Objective To study the effects of thymus transplantation(TT)combined with CD4--DLI on T cell reconstitution after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods BALB/c mice were randomly divided into three groups:hematopoietic stem cell transplantation (HSCT group),hematopoietic stem cell transplantation combined with thymus transplantation(TT group)and hematopoietic stem cell transplanta-tion combined with thymus transplantation plus CD4+ T cell-depleted lymphocyte infusion(CD4--DLI group). On day-1,the mice were treated with the lethal dose of radiotherapy. On day 0,C57BL/6 mice were used as donor for hematopoietic stem cell transplantation. The mice were sacrificed on 5 days,2 weeks,4 weeks and 3 months after transplantation,respectively. The peripheral blood and spleen cells of mice were collected for determinations of T cell surface antigen,T cell receptor,naive T cells and intracellular cytokines. HE staining was used to assess the development of donor thymus. Results TT and CD4--DLI did not impair each other′s effects on T cell reconstitu-tion. TT combined with CD4--DLI increased the number of T cell reconstruction. CD4--DLI promoted the effect of TT on enlargement naive CD4+and CD8+T cell pool. Combination of TT and CD4--DLI enhanced the cytokine pro-duction of T cells. Conclusion TT combined with CD4--DLI had no side effects on TCR repertoire and thymus. Conclusion TT combined with CD4--DLI can enhance the reconstitution of T cell number and function via thymus dependent and thymus independent mechanism.

OBJECTIVE: To construct and obtain ideal protein delivery vectors by researching the delivery efficiency and cytotoxicity to Hela cells using mPEG-PLGA-BSA-FITC-NPs. METHOD: The mPEG-PLGA nanoparticle was obtained through surface modification of PLGA with PEG, and deliver BSA-FITC into Hela cells in vitro. The positive cells were counted by Laser scanning confocal microscopy and the survival rate of Hela cells was calculated by MTT assay at different time points. RESULT: mPEG-PLGA-BSA-FITC-NPs shows the classic nanometer size, and the encapsulation efficiency reached 51. 2%. At the same time, the nanoparticles possess characteristics of slow release. By optimizing the delivery conditions, the highest efficiency of mPEG-PLGA-BSA-FITC-NPs was above 65.2%, and the cellular viability was about 85.7%. CONCLUSION mPEG-PLGA-BSA-FITC-NPs nanoparticles can successfully carry the target protein into cells as safe and effective as novel delivery materials of protein in vitro, and has shown slow release characteristics. The mPEG-PLGA-BSA-FITC-NPs provide ideal delivery vector for future application in clinical treatment of disease using nano-materials.
Drug Carriers ; Fluorescein-5-isothiocyanate ; analogs & derivatives ; HeLa Cells ; Humans ; Nanoparticles ; Particle Size ; Polyesters ; Polyethylene Glycols ; Serum Albumin, Bovine

BACKGROUND:There are myoblasts in human embryonic skeletal muscle. It remains poorly understand whether myoblasts in vitro can form myotube and what are the corresponding markers for identifying myoblasts and myotubes. OBJECTIVE:To investigate whether in vitro cultured myoblasts from human embryonic skeletal muscle can form myotube and whether they can express neural markers. METHODS:Human embryonic muscle-derived myoblasts were cultured in serum-containing medium. When the primary culture was established, cultured cel s were identified with immunocytochemistry for neural markers, such asβ-tubulin markers (desmin, myogenin, smooth muscle actin and myosin). RESULTS AND CONCLUSION:A population of myoblasts could migrate from human embryonic muscle tissues. They could express the markers for skeletal muscle such as desmin and myogenin, and they could express neuron specific enolase, nestin and neurofilament 200. They could form myotubes in vitro, and myotubes expressedβⅢ-tubulin, neurofilament 200 and glial fibril ary acidic protein. The data support the hypothesis that myoblasts from human embryonic muscle express neural markers and muscle markers, and cultured myoblasts and myotubes expressed neuron specific enolase,β-tubulin Ⅲ, nestin, neurofilament 200 and glial fibrillary acidic protein. This indicates that these markers could not be used for cel identification of trans-differentiation study from muscle origin to nervous system.